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Boyd, B.

Publications and source records attributed to Boyd, B..

4 recordsLinked to original sources

Liquid crystalline mesophase spacing as a quantitative predictor of release kinetics for co-loaded hydrophilic and hydrophobic payloads

Liquid crystalline mesophases exhibit structurally programmable internal architectures that enable co-loading of chemically orthogonal molecules within a single composite material. Realizing the potential of these materials for drug delivery requires a quantitative understanding of how tuning the composition affects internal mesophase architecture and consequently performance metrics such as payload release. Here, Flash NanoPrecipitation with hydrophobic ion pairing is used to prepare nanocarriers containing liquid crystalline mesophases co-encapsulating two compounds from widely different chemical classes: hydrophilic polymyxin B (logP -6) with one of four hydrophobic co-core materials (logP 7-11), achieving >75% encapsulation efficiency and up to 32% and 50% mass loadings for polymyxin and co-core. Synchrotron SAXS is used to quantify characteristic mesophase repeat spacing, which is found to be tunable as a function of composition. A strong correlation between d-spacing and polymyxin release rate is presented. Co-core chemistry and weight fraction jointly govern mesophase architecture, and repeat distance emerges as a structural metric linking these to the hydrophilic payload release kinetics. Mucus diffusivity and antibacterial efficacy are assessed as independent performance metrics, and results corroborate the release behavior. These findings establish a quantitative framework connecting material composition, mesophase architecture, and functional performance that can be applied toward rational co-formulation design. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/734853v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@a0c38eorg.highwire.dtl.DTLVardef@86d33eorg.highwire.dtl.DTLVardef@196c83dorg.highwire.dtl.DTLVardef@3423c3_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOToC Graphic TextC_FLOATNO Flash NanoPrecipitation yields liquid crystalline nanocarriers co-encapsulating with high efficiency payloads with widely distinct physicochemical properties. Synchrotron SAXS establishes characteristic repeat spacing as a quantitative structural metric directly governing hydrophilic release kinetics, providing a rational design framework linking mesophase architecture to functional performance across a range of payload structures. C_FIG

bioengineering↗

eIF4E assembly into C. elegans germ granules is essential for its repressive function

Metazoan germ cells form intracellular germ granules, cytoplasmic RNA-protein condensates that contain a variety of RNAs and proteins essential for germline identity, maintenance, and fertility. P granules are a type of C. elegans germ granule proposed to be sites of mRNA repression. Proper P granule assembly is dependent on PGL-1 and its granule-forming protein relatives. Numerous RNA-binding proteins localize to P granules, like the eIF4E mRNA cap binding homolog, IFE-1. IFE-1 directly interacts with PGL-1 in vivo and in vitro. The molecular function of P granules remains enigmatic. Here, PGL-1 was molecularly dissected in vivo to determine protein regions required for P granule assembly, binding partner recruitment, and germ cell development. A specific region in the PGL-1 C-terminus was necessary and sufficient for IFE-1 recruitment to P granules and for fertility. IFE-1 RNA targets were identified, and reporters of top gene targets were repressed in the adult germline. This repression was dependent on PGL-1 and its IFE-1 binding peptide. These findings provide evidence that IFE-1 and P granules are a factor and site of mRNA repression, respectively. This repression required IFE-1 assembly into P granules, supporting the model that RNA-protein condensate assembly is necessary for its biological and biochemical functions.

developmental biology↗

Exogenous expression of a histone H3.3 isoform causes extranuclear divisions in the C. elegans intestine

Histone proteins condense DNA into chromatin and play significant roles in gene regulation. Mutations that alter histone function can disrupt critical gene expression programs and are implicated in driving cancer and other human diseases. Most mechanistic research on histones has been conducted in cell culture, mitotic tissues, or animal disease models rather than in normal tissue. Caenorhabditis elegans is a model organism with a well-established developmental program and conserved histone mechanisms shared with other metazoans. Prior work generated several single-copy histone reporters expressing exogenous histone protein in the intestine. Surprisingly, the histone H3.3 reporter worms possessed extra nuclei in the anterior intestine. This phenotype was incompletely penetrant and arose early during larval development. Mutations predicted to perturb histone H3.3 reporter expression or deposition into chromatin ameliorated the phenotype. DNA Fluorescence In situ Hybridization (FISH) was used to measure chromosome copy number and revealed approximately half the DNA content in the extra nuclei versus undivided controls, suggesting aberrant nuclear division during normal rounds of intestinal endoreduplication. Thus, these reporters serendipitously identified a distinct function of histone H3.3 in triggering aberrant nuclear division during animal development. Other histone isoforms may have previously unrecognized biological functions in terminally differentiated tissue alongside their roles in mitotic tissue.

developmental biology↗

Pandora: 4-D white matter bundle population-based atlasesderived from diffusion MRI fiber tractography

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate. While few white matter atlases do exist based on diffusion MRI fiber tractography, they are often limited to descriptions of white matter as spatially separate "regions" rather than as white matter "bundles" or fascicles, which are well-known to overlap throughout the brain. Additional limitations include small sample sizes, few white matter pathways, and the use of outdated diffusion models and techniques. Here, we present a new population-based collection of white matter atlases represented in both volumetric and surface coordinates in a standard space. These atlases are based on 2443 subjects, and include 216 white matter bundles derived from 6 different state-of-the-art tractography techniques. This atlas is freely available and will be a useful resource for parcellation and segmentation.

neuroscience↗